This invention relates to antiinflammatory diaryl thiophenes.
A number of references, such as Compt. Rend., 242, 1738 (1956) and Z. Chem., 13, 57 (1973), disclose the preparation of 2,3-diarylthiophenes.
M. G. Reinecke, et al., in J. Chem. Soc., Chem. Commun., 585 (1980) disclose the gas phase thermolysis of 2,3-thiophenedicarboxylic anhydride in the presence of pentafluoroacetone and hexafluoroacetone followed by acidic hydrolysis to give 2-[.alpha.-difluoromethyl-.alpha.-(trifluoromethyl)hydroxymethyl]thiophene -3-carboxylic acid and 2-[.alpha.,.alpha.-bis(trifluoromethyl)hydroxymethyl]thiophene-3-carboxyli c acid respectively. The latter was also prepared by lithiation of N,N-diethyl-3-thiophene carboxamide followed by reaction with hexafluoroacetone and acid hydrolysis. No biological activity is reported for any of these compounds.
D. C. England in U.S. Pat. No. 3,197,480 discloses .alpha.,.alpha.-bis(trifluoromethyl)pyrrole-2-methanol. Pharmaceutical use for the compounds of this patent is not disclosed.
There is a continuing need for safe and effective antiinflammatory agents. Inflammation is a disease process characterized by redness, fever, swelling, and pain. Arthritis, in its various forms, is the most prevalent, chronic, and severe of the inflammatory diseases. Traumatic injury and infection also involve inflammation, and antiinflammatory drugs are often used in their treatment. The usefulness of most commercial antiinflammatories is limited because of toxicity and adverse side-effects. Many produce gastric irritation and other effects, such as changes in blood cells and central nervous system. Adrenocortical steroids produce gastric irritation and suppression of normal adrenal function.
The present invention results from efforts to develop new antiarthritic compounds with good antiinflammatory activity and minimal side effects that could be more effective in treating arthritis than presently available drugs.
In addition to antiinflammatory properties, some compounds of this invention have analgesic activity. This additional property is desirable in treatment of arthritis or related diseases; however, such compounds can be employed solely to alleviate pain.